Ventilation method and control of a ventilator based on same

ABSTRACT

The invention provides an improved ventilation method and method for controlling a ventilator apparatus in accordance with same. More specifically, the present invention relates to a method of controlling a ventilator apparatus comprising the steps of placing a ventilator in a mode capable of adjusting airway pressure (P) and time (T), monitoring expiratory gas flow, analyzing the expiratory gas flow over time (T) to establish an expiratory gas flow pattern, and setting and/or adjusting a low time (T 2 ) based on the expiratory gas flow pattern. Alternatively, the present invention relates to a method of controlling a ventilator apparatus comprising the steps of placing a ventilator in a mode capable of adjusting airway pressure (P) and time (T), and setting a low airway pressure (P 2 ) of substantially zero cmH 2 O.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/176,710 filed Jun. 20, 2002, which claims priority to U.S.Provisional Application No. 60/299,928 filed Jun. 21, 2001.

FIELD OF THE INVENTION

The invention relates to the field of ventilating human patients. Moreparticularly, the present invention relates to an improved method forinitiation, management and/or weaning of airway pressure releaseventilation and for controlling a ventilator in accordance with same.

BACKGROUND OF THE INVENTION

Airway pressure release ventilation (APRV) is a mode of ventilationbelieved to offer advantages as a lung protective ventilator strategy.APRV is a form of continuous positive airway pressure (CPAP) with anintermittent release phase from a preset CPAP level. APRV allowsmaintenance of substantially constant airway pressure to optimize endinspiratory pressure and lung recruitment. The CPAP level optimizes lungrecruitment to prevent or limit low volume lung injury. In addition, theCPAP level provides a preset pressure limit to prevent or limit overdistension and high volume lung injury. The intermittent release fromthe CPAP level augments alveolar ventilation. Intermittent CPAP releaseaccomplishes ventilation by lowering airway pressure. In contrast,conventional ventilation elevates airway pressure for tidal ventilation.Elevating airway pressure for ventilation increases lung volume towardstotal lung capacity (TLC), approaching or exceeding the upper inflectionpoint. Limiting ventilation below the upper inflection of the P-V(airway pressure versus volume) curve is one of the goals of lungprotective strategies. Subsequently, tidal volume reduction is necessaryto limit the potential for over distension. Tidal volume reductionproduces alveolar hypoventilation and elevated carbon dioxide levels.Reduced alveolar ventilation from tidal volume reduction has lead to astrategy to increase respiratory frequency to avoid the adverse effectsof hypercapnia. However, increased respiratory frequency is associatedwith increase lung injury. In addition, increase in respiratoryfrequency decreases inspiratory time and the potential for recruitment.Furthermore, increasing respiratory frequency increases frequencydependency and decreases potential to perform ventilation on theexpiratory limb of the P-V curve.

During APRV, ventilation occurs on the expiratory limb. The resultantexpiratory tidal volume decreases lung volume, eliminating the need toelevate end inspiratory pressure above the upper inflection point.Therefore, tidal volume reduction is unnecessary. CPAP levels can be setwith the goal of optimizing recruitment without increasing the potentialfor over distension. Consequently, end inspiratory pressure can belimited despite more complete recruitment and ventilation can bemaintained.

Airway pressure release ventilation (APRV) was developed to provideventilator support to patients with respiratory failure. Clinical use ofAPRV is associated with decreased airway pressures, decreased dead spaceventilation and lower intra-pulmonary shunting as compared toconventional volume and pressure cycled ventilation. APRV limitsexcessive distension of lung units, thereby decreasing the potential forventilator induced lung injury (VILI), a form of lung stress. Inaddition, APRV reduces minute ventilation requirements, allowsspontaneous breathing efforts and improves cardiac output. APRV is alsoassociated with reduction or elimination of sedative, inotropic andneuromuscular blocking agents.

APRV is a form of positive pressure ventilation that augments alveolarventilation and lowers peak airway pressure. Published data on APRV hasdocumented airway pressure reduction on the order of 30 to 75 percentover conventional volume and pressure cycled ventilation duringexperimental and clinical studies. Such reduction of airway pressure mayreduce the risk of VILI. APRV improves ventilation to perfusion ratio(V_(A)/Q) matching and reduces shunt fraction compared to conventionalventilation. Studies performed utilizing multiple inert gas dilution andexcretion technique (MIGET) have demonstrated less shunt fraction, anddead space ventilation. Such studies suggest that APRV is associatedwith more uniform distribution of inspired gas and less dead spaceventilation than conventional positive pressure ventilation.

APRV has been associated with improved hemodynamics. In a 10-year reviewof APRV, Calzia reported no adverse hernodynamic effects. Severalstudies have documented improved cardiac output, blood pressure andoxygen delivery. Consideration of APRV as an alternative topharmacological or fluid therapy in the hemodynamically-compromised,mechanically-ventilated patient has been recommended in several casereports.

APRV is a spontaneous mode of ventilation which allows unrestrictedbreathing effort at any time during the ventilator cycle. Spontaneousbreathing in Acute Respiratory Distress Syndrome/Acute Lung Injury(ALI/ARDS) has been associated with improved ventilation and perfusion,decreased dead space ventilation and improved cardiac output and oxygendelivery. ALI/ARDS is a pathological condition characterized by markedincrease in respiratory elastance and resistance. However, most patientswith ALI/ARDS exhibit expiratory flow limitations. Expiratory flowlimitations results in dynamic hyperinflation and intrinsic positive endexpiratory pressure (PEEP) development. In addition, ARDS patientsexperience increased flow resistance from external ventilator valvingand gas flow path circuitry including the endotracheal tube and theexternal application of PEEP.

Several mechanisms can induce expiratory flow limitations in ALI/ARDS.In ALI/ARDS both FRC and expiratory flow reserve is reduced. Pulmonaryedema development and superimposed pressure result in increased airwayclosing volume and trapped volume. In addition, the reduced number offunctional lung units (de-recruited lung units and enhanced airwayclosure) decrease expiratory flow reserve further. Low volumeventilation promotes small airway closure and gas trapping. In addition,elevated levels of PEEP increase expiratory flow resistance. In additionto downstream resistance, maximal expiratory flow depends on lungvolume. The elastic recoil pressure stored in the proceeding lunginflation determines the rate of passive lung deflation.

APRV expiratory flow is enhanced by utilization of an open breathingsystem and use of low (0-5 cmH₂O) end expiratory pressure. Ventilationon the expiratory limb of the P-V curve allows lower PEEP levels toprevent airway closure. Lower PEEP levels result when PEEP is utilizedto prevent de-recruitment rather than attempting partial recruitment.Increasing PEEP levels increases expiratory resistance, conversely lowerPEEP reduce expiratory resistance, thereby accelerating expiratory flowrates. Sustained inflation results in increased lung recruitment(increased functional lung units and increased recoil pressure) andventilation along the expiratory limb (reduced PEEP and expiratory flowresistance), improving expiratory flow reserve. In addition, releasefrom a sustained high volume increases stored energy and recoilpotential, further accelerating expiratory flow rates. Unlike low volumeventilation, release from a high lung volume increases airway caliberand reduces downstream resistance. Maintenance of end expiratory lungvolume (EELV) to inflection point of the flow volume curve and the useof an open system allows reduction in circuitry flow resistance. EELV ismaintained by limiting the release time and titrated to the inflectionpoint of the flow volume curve. Reduced levels of end expiratorypressure are required when ventilation occurs on the expiratory limb ofthe P-V curve. In ALI/ARDS, increased capillary permeability results inlung edema. Exudation from the intravascular space accumulates, andsuperimposed pressure on dependent lung regions increases and compressesairspaces. Dependent airspace collapse and compressive atelectasisresults in severe V_(A)/Q mismatching and shunting. Regionaltranspulmonary pressure gradients which exist in the normal lung areexaggerated during the edematous phase of ALI/ARDS. Patients typicallybeing in the supine position, forces directed dorsally and cephaladprogressively increase pleural pressures in dependent lung regions.Ventilation decreases as pleural pressure surrounding the dependentregions lowers transalveolar pressure differentials. Full ventilatorysupport during controlled ventilation promotes formation of dependentatelectasis, increase V_(A)/Q mismatching and intrapulmonary shunting.Increasing airway pressure can re-establish dependent trans-pulmonarypressure differential but at the risk of over distension of nondependentlung units. Alternatively, spontaneous breathing, as with APRV, canincrease dependent transpulmonary pressure differentials withoutincreasing airway pressure.

APRV allows unrestricted spontaneous breathing during any phase of themechanical ventilator cycle. As noted, spontaneous breathing can lowerpleural pressure, thereby increasing dependent transpulmonary pressuregradients without additional airway pressure. Increasing dependenttranspulmonary pressure gradients improves recruitment and decreasesV_(A)/Q mismatching and shunt. As compared to pressure supportventilation (PSV) multiple inert gas dilution technique, APRV providesspontaneous breathing and improved V_(A)/Q matching, intrapulmonaryshunting and dead space. In addition, APRV with spontaneous breathingincreased cardiac output. However, spontaneous breathing during pressuresupport ventilation was not associated with improved V_(A)/Q matching inthe dependent lung units. PSV required significant increases in pressuresupport levels (airway pressure) to match the same minute ventilation.

Conventional lung protective strategies are associated with increaseduse of sedative agents and neuromuscular blocking agents (NMBA). Theincreased use of sedative and NMBA may increase the time the patientmust remain on mechanical ventilation (“vent days”) and increasecomplications. NMBA are associated with prolonged paralysis andpotential for nosocomial pneumonia. APRV is a form of CPAP and requiresspontaneous breathing.

Decreased usage of sedation and neuromuscular blocking agents (NMBA) hasbeen reported with APRV. In some institutions, APRV has nearlyeliminated the use of NMBA, resulting in a significant reduction in drugcosts. In addition to drug cost reduction, elimination of NMBA isthought to reduce the likelihood of associated complications such asprolonged paralysis and may facilitate weaning from mechanicalventilation.

Mechanical ventilation remains the mainstay management for acuterespiratory failure. However, recent studies suggest that mechanicalventilation may produce, sustain or increase the risk of acute lunginjury (ALI). Ventilator induced lung injury (VILI) is a form of lungstress failure associated with mechanical ventilation and acute lunginjury. Animal data suggest that lung stress failure from VILI mayresult from high or low volume ventilation. High volume stress failureis a type of stretch injury, resulting from over distension ofairspaces. In contrast, shear force stress from repetitive airwayclosure during the tidal cycle from mechanical ventilation results inlow volume lung injury.

Initially, lung protective strategy focused on low tidal volumeventilation to limit excessive distension and VILI. Amato in 1995 and in1998 utilized lung protective strategy based on the pressure-volume(P-V) curve of the respiratory system. Low tidal volumes (6 ml/kg)confined ventilation between the upper and lower inflection points ofthe P-V curve. End expiratory lung volume was maintained by setting PEEPlevels to 2 cmH₂O above the lower inflection point. Amato demonstratedimproved survival and increased ventilator free days.

However, subsequent studies by Stewart and Bower were unable todemonstrate improved survival or ventilator free days utilizing lowtidal volume ventilation strategy. Unlike Stewart and Bower, Amatoutilized elevated end expiratory pressure in addition to tidal volumereduction. Such important differences between these studies limitedconclusions as to the effectiveness of low tidal ventilation limitingventilator associated lung injury (VALI).

Recent completion of the large controlled randomized ARDSNet trialdocumented improved survival and ventilator free days utilizing lowtidal volume ventilation (6 ml/kg) vs. traditional tidal volumeventilation (12 ml/kg). Although the low tidal volume group (6 ml/kg)and traditional tidal volume group (12 ml/kg) groups utilized identicalPEEP/FiO₂ scales, PEEP levels were significantly higher in the low tidalvolume group. Higher PEEP levels were required in the low tidal volumegroup in order to meet oxygenation goals of the study. Despite improvedsurvival in the low tidal volume group (6 ml/kg) over traditional tidalvolume group (12 ml/kg), survival was higher in the Amato study. TheARDSNet trial also failed to demonstrate any difference in the incidenceof barotrauma. The higher PEEP requirements and the potential forsignificant intrinsic PEEP from higher respiratory frequency in thelower tidal volume group, may have obscured potential contribution ofelevated end expiratory pressure on survival. Further studies arecontemplated to address the issue of elevated end expiratory pressure.

In the prior art, utilization of the quasi-static inspiratory pressureversus volume (P-V) curve has been advocated as the basis forcontrolling a ventilator to carry out mechanical ventilation. The shapeof the inspiratory P-V curve is sigmoidal and is described as havingthree segments. The curve forms an upward concavity at low inflationpressure and a downward concavity at higher inflation pressures. Betweenthe lower concavity and the upper concavity is the “linear” portion ofthe curve. The pressure point resulting in rapid transition to thelinear portion of the curve has been termed the “lower inflectionpoint”. The lower inflection point is thought to represent recruitmentof atelectatic alveolar units. The increasing slope of the P-V curveabove lower inflection point reflects alveolar compliance. Above theinflection point, the majority of air spaces are opened or “recruited”.Utilizing the lower inflection point of the inspiratory P-V curve plus 2cmH₂O has been proposed to optimize alveolar recruitment. Optimizinglung recruitment prevents tidal recruitment/de-recruitment and cyclicairway closure at end expiration. Ultimately, optimizing lungrecruitment could potentially reduce shear force generation and lowvolume lung injury.

SUMMARY OF THE INVENTION

The invention provides an improved ventilation method and method forcontrolling a ventilator apparatus in accordance with same. Theinvention recognizes that ventilation utilizing elevated PEEP levelprevents low volume lung injury. Setting PEEP levels above theinflection point of the expiratory flow curve is based on the notionthat, at this level of PEEP, the majority of the airways are opened orrecruited. In addition, this level of PEEP is thought to prevent airwayclosure or de-recruitment. Specifically, lung volume (V_(L)) increase atthe level of inflection is thought to be related to increases inalveolar number (V_(N)) (recruitment). Thereafter the steeper inflectionrepresents compliance of the recruited airspaces; the resulting lungvolume increase is secondary to increase in alveolar volume (V_(A))(non-recruitment volume change). The invention also recognizes that theP-V curve may not be a reliable indicator of recruitment. The P-V curverepresents the entire respiratory system and may not adequately reflectthe individual air spaces. Optimal PEEP levels at which cyclic airwayclosure is prevented are not yet precisely known, but are unlikely to berepresented by a single point as contemplated in the prior art. Theinventor believes it is more likely that recruitment occurs over a widerange of pressures. Furthermore, utilization of the inspiratory limb ofthe P-V curve may be of limited value in determining optimal PEEPlevels. Events during recording of the P-V trace may affect thepressure-volume relationship. PEEP-induced recruitment may affect theslope of the P-V curve.

The invention further recognizes that recruitment continues above theinflection point and may continue at airway pressures beyond 30 cmH2Oand that the primary mechanism of lung volume change may berecruitment/de-recruitment (R/D) rather than isotropic and anisotropicalveolar volume change. Lung volume change to 80% of total lung capacity(TLC) may well be a result of alveolar number increase (R/D) rather thanalveolar size. Furthermore, recruitment is an end inspiratory phenomenonand may be more closely related to plateau pressure rather than PEEP.Therefore, to prevent tidal recruitment/de-recruitment (RID), cyclicshear stress and low volume lung injury, the invention contemplates thathigher pressure may be required to achieve complete recruitment. It isrecognized that if PEEP levels are set to end inspiratory pressure inorder to completely recruit the lung, the superimposition of tidalventilation could result in over-distension and high volume lung injurydespite tidal volume reduction.

Accordingly, the invention recognizes that recruitment is an inflationphenomenon which continues beyond conventional PEEP levels. Recruitmentrequires enough pressure to overcome threshold-opening pressures and thesuperimposed pressure of the airspace. Plateau pressure or continuouspositive airway pressure (CPAP) rather than PEEP level may be moreappropriate determinants of full lung recruitment. PEEP conceptuallyprevents de-recruitment after a sustained inflation. Airway closure orde-recruitment is a deflation phenomenon. Therefore, in accordance withthe invention, PEEP may be more suitable set to the inflection point ofthe deflation limb of the P-V curve rather than that of the inflationlimb.

The deflation limb of the pressure volume curve reflects the differencesbetween opening and closing pressures of airspaces (hysteresis). Higherairway pressures are necessary to open airspaces than are required toprevent airspaces closure. In pulmonary edema states, such as ALI/ARDS,the inflation limb of the P-V curve develops an increasedpressure-volume relationship. Increased opening pressure results ingreater pressure requirements for airspace opening. However, thedeflation limb maintains a preserved pressure-volume relationshipdespite increasing pulmonary edema. Greater hysteresis results from adownward and right displacement of the inflation limb of the P-V curve.Therefore, ventilator control based on PEEP should be used to preventairway closure rather than to cause airway opening. Using the deflationlimb of the P-V curve is believed to have advantages for ventilation.Ventilation occurring on the more favorable pressure-volume relationshipof the deflation curve reduces the level of PEEP required to prevent thesame degree of airway closure (de-recruitment).

Rather than PEEP, plateau or CPAP levels should be utilized for bringingabout airway opening (recruitment), allowing substantially completerecruitment. In addition to adequate threshold pressure, completerecruitment requires constant inflation in order to sustain recruitment.Furthermore, sustained recruitment facilitates ventilation on thedeflation limb. Ventilation occurs on the deflation limb of the P-Vcurve only after a sustained recruitment maneuver. Sustained inflationpushes the P-V curve to the outer envelope on to the deflation limb.During the sustained inflation, the lung undergoes stress relaxation.Stress relaxation accounts for a pressure reduction on the order of 20%within the initial 4 seconds of inflation.

In accordance with the invention, APRV mode ventilation is establishedbased on an initial set of ventilation parameters selected as describedin further detail below. Once ventilation has been initiated, theparameter, T2, which defines the duration of the ventilator releasephase, is monitored and adjusted according to at least one andpreferably several alternative methods.

One method is to measure the expiratory gas flow rate during expirationand to adjust T2, if necessary, such that T2 is terminated when the rateof expiratory gas flow is at a value of about 25% to 50% of its absolutepeak value during expiration. To achieve this, the ventilator iscontrolled to monitor the expiratory gas flow rate and terminate therelease phase when the flow rate reaches a value within theaforementioned range.

Another method is to monitor expiratory flow and determine, based on theflow pattern, whether the flow is of a restrictive or obstructivenature, and adjust T2 accordingly. More particularly, T2 would beadjusted to a value of less than about 0.7 seconds in the event ofrestrictive flow and to a value greater than about 0.7 seconds in theevent of obstructive flow. According to yet another method, theexpiratory flow is monitored for the presence of an inflection point andT2 is adjusted as required to substantially eliminate or at least reducethe inflection point.

During management of ventilation in accordance with the invention bloodoxygen and carbon dioxide levels are monitored. In the event ofhypercarbia, the highest airway pressure achieved during inspiration(P1) and the duration of the positive pressure phase (T1) are bothincrementally increased substantially contemporaneously once or more asneeded until blood carbon dioxide declines to an acceptable level.Oxygenation is also regulated by adjusting P1 and T1 in a particularmanner as will be described.

According to yet another aspect of the invention, weaning fromventilation is carried out by initiating a series of successivereductions in P1, each of which is accompanied by a substantiallycontemporaneous, increase in the duration of inspiration T1 such thatover time, ventilation is transitioned from APRV to a substantially CPAPmode.

Applicant's ventilation method and method for controlling a ventilationapparatus based on same provides significant advantages over the priorart. These advantages include an increase in vent free days, lowerventilator-related drug costs, reduced ventilator associatedcomplications, reduced likelihood of high volume lung injury, andreduced likelihood of low volume lung injury. These and other objectsand advantages of the invention will become more apparent to a person ofordinary skill in the art in light of the following detailed descriptionand appended drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart illustrating a preferred embodiment of aventilation method and control of a ventilator based on same accordingto the invention;

FIG. 2 is a schematic airway pressure versus time tracing for airwaypressure release ventilation;

FIG. 3 is a airway pressure versus time tracing during the inspiratory(P1) phase of ventilation;

FIG. 4 is an airway volume versus pressure curve illustrating a shiftfrom the inspiratory limb to the expiratory limb thereof;

FIG. 5 is an inspiratory and expiratory gas flow versus time tracing forairway pressure release ventilation;

FIG. 6 is an expiratory gas flow versus time tracing;

FIG. 7 is a set of expiratory gas flow versus time tracing illustratingdetermination of whether flow pattern is normal, restrictive orobstructive based on the shape of the tracing, and

FIG. 8 is a set of airway pressure versus time tracings illustratingventilation weaning by successive reductions in pressure P1 andsubstantially contemporaneous increases in time T1.

DETAILED DESCRIPTION

A patient in need of ventilation is intubated and connected to amechanical ventilator which, except for being controlled in accordancewith the present invention as described herein, can be of an otherwiseknown type such as the model known as Evita 4 distributed by DraegerMedical, Inc. of Telford, Pa. The ventilator includes pumps, valves andpiping as well as all pressure, flow and gas content sensors required tocarry out the invention. Operation of the ventilator is governed by acontrol unit which includes one or more processors. The control unitalso includes both volatile and non-volatile electronic memory for thestorage of operating programs and data. An operator interface coupled tothe control unit typically includes a graphical user interface as wellas a keyboard and/or pointing device to enable an operator to select theoperating mode of the ventilator and/or to enter or edit patient dataand operating parameters such as the pressures, times, flows, and/orvolumes associated with one or more ventilation cycles. The interfacealso permits display, via a monitor, of measurements, trends or otherdata in alphanumeric and/or graphical format. The ventilator alsoincludes a variety of sensors disposed in the ventilation gas circuitand/or elsewhere for measuring ventilation parameters including airwayflow, airway pressure, and the makeup of inspiratory gasses, expiratorygasses and/or blood gasses including the partial pressures of oxygen andcarbon dioxide in the bloodstream of the patient and the level of oxygensaturation of the blood. Based on pressure and flow measurements, thecontroller of the ventilator is also capable of calculating inspiratoryand expiratory gas volumes. In addition, the control unit of theventilator includes the capability to process data generated based oninputs from the sensors and determine variety parameters. For example,the ventilator can determine the ratio of inspiratory to expiratoryeffort based on flow measurements generated by flow meters associatedwith its inspiratory and expiratory valves. Such ratio is useful as anindicator of lung volume.

Referring to FIG. 1, the invention contemplates initiating ventilationof a patient in an APRV mode based on initial oxygenation andventilation settings. The airway pressure during expiration (P2) issubstantially zero throughout ventilation to allow for the rapidacceleration of expiratory gas flow rates. Typically, the fraction ofoxygen in the inspired gas (FiO2) is initially set at about 0.5 to 1.0(i.e. about 50% to 100%). The highest airway pressure achieved duringinspiration (P1) must be sufficiently high to overcome airspace closingforces and initiate recruitment of lung volume. P1 may suitably beinitialized at a default value of about 35 cmH2O. Alternatively, P1 maybe established based either on the severity and type of lung injury orbased on recruitment pressure requirements. The latter method ispreferred in cases where the ventilation/perfusion ratio is less than orequal to about two hundred millimeters of mercury (200 mmHg). Theventilation perfusion ratio is preferably monitored continuously. It isthe ratio of the partial pressure of oxygen in the blood of the patientto the fraction of oxygen present in the inspired gas (i.e. PaO2/FiO2but is commonly abbreviated as P/F).

Where the type and severity of lung injury are characterized by a P/F ofgreater than about 350 mmHg, an initial value of P1 within the range ofabout 20 cmH2O to 28 cmH2O is preferably established. On the other hand,if the P/F ratio is less than about 350 mmHg, P1 is preferablyinitialized within the range of about 28 cmH2O to 35 cmH2O.

In situations where the P/F ratio is less than or equal to about 200mmHg, such as may occur where the patient's initial injury isnon-pulmonary and/or lung injury is of an indirect nature, the inventioncontemplates establishment of P1 at a value of between about 35 mmHg and40 mmHg but preferably not appreciably above 40 mmHg. In cases where P1is initially established at a default value of about 35 cmH2O, P1 isreduced from such a value once P/F exceeds about 250 mmHg. Initiation ofventilation also requires the establishment of time (duration) settingsfor inspiration and expiration.

Initially, the duration of the positive pressure phase (T1) isestablished at a value within the range of about 5.0 to about 6.0seconds unless the measured PaCO2 is greater than about 60 mmHg. In thatcase, T1 is more preferably set to a lower initial value of within therange of about 4.0 to 5.0 seconds. The duration of the ventilatorrelease phase (T2) may suitably be initialized at a value within therange of 0.5 to 0.8 seconds with about 0.7 seconds being a preferreddefault value.

Once initial values of P1, P2, T1 and T2 have been established,ventilation continues in a repetitive APRV mode cycle generally asillustrated in FIG. 2. During management of ventilation in accordancewith the invention, the initial values of one or more of theseparameters are re-assessed and modified in accordance with measuredparameters as will now be described with continued reference to FIG. 1.

In management of ventilation in accordance with the invention, aprincipal goal is to maintain the level of carbon dioxide in the bloodof the ventilated patient (PaCo2) at a level of less than or equal toabout 50 mmHg. Toward that end, arterial PaCO2 is monitored continuouslyor measured as clinically indicated and the ventilator controlled toadjust ventilation as follows. Any time after ventilation has commenced,but preferably soon thereafter or promptly upon any indication ofhypercarbia (PaCO2 above about 50 mmHg), the setting of T2 is optionallybut preferably checked and re-adjusted if necessary. According to theinvention, optimal end expiratory lung volume is maintained by titrationof the duration of the expiration or release phase by terminating T2based on expiratory gas flow. To do so, the flow rate of the expiratorygas is measured by the ventilator and checked in relation to the time atwhich the controller of the ventilator initiates termination of therelease phase. The expiratory exhaust valve should be actuated toterminate the release phase T2, at a time when the flow rate of theexpiratory gas has decreased to about 25% to 50% of its absolute peakexpiratory flow rate (PEFR). An example is illustrated in FIG. 5. Inthat example, T2 (sometimes referred to as Tlow) terminates bycontrolling the expiratory exhaust valve to terminate the release phasewhen the expiratory gas flow rate diminishes to 40% PEFR.

If monitoring of PaCO2 indicates hypocarbia is present (i.e. PaCO2 lessthan about 50 mmHg), T1 is increased by about 0.5 seconds whilemaintaining P1 substantially unchanged. Should the patient remainhypocarbic as indicated by subsequent measure of PaCO2, weaning in themanner to be described may be initiated provided oxygenation issatisfactory and weaning is not otherwise contraindicated based oncriteria to be described further below.

The hypercarbic patient though is not to be weaned. In the event ofhypercarbia, the invention contemplates assessment of the expiratoryflow pattern before making significant further adjustments toventilation parameters. This assessment can readily be carried out by asoftware program stored within the control unit of the ventilator whichcarries out automated analysis of the expiration flow versus timetracing. As illustrated in FIG. 7, normal expiratory flow ischaracterized by flow which declines substantially monotonically fromthe onset of the release phase through its termination and does not falloff prematurely or abruptly. Restrictive flow in contrast declinesrapidly from the onset of the release phase to zero or a relativelysmall value. Obstructive flow tends to be more extended in duration andis characterized by an inflection point beyond which the rate of flowfalls off markedly from its initial rate. FIG. 6 illustrates anotherexample of an obstructive flow pattern. Based on analysis of flow dataprovided by expiratory flow sensors, the control unit of the ventilatoris programmed to determine whether flow is obstructive or restrictivebased on the characteristics just described. If it is determined thatobstructive or restrictive flow is present, the invention contemplatesadjusting T2 before making any other significant adjustments toventilation parameters. This can be done according to either of twoalternative methods.

One method is to adjust T2 to a predetermined value according to whetherflow is either obstructive or restrictive but allowing T2 to remain atits previous value if flow is normal. In the case of restrictive flow,T2 should be adjusted to less than about 0.7 seconds. On the other hand,obstructive flow calls for a T2 of greater duration, preferably greaterthan about 0.7 seconds with 1.0 to 1.2 being typical.

As FIG. 1 indicates, it is optional but advisable to promptly assess thesedation level of the hypercarbic patient. Sedation of the patient canbe evaluated by any suitable technique such as the conventional clinicaltechnique of determining an SAS score for the patient. If the patientappears over-sedated based on the SAS score (SAS score greater thanabout 2) or otherwise, reduction of sedation should be considered andinitiated if appropriate. Thereafter, as FIG. 1 indicates, T1 should beincreased by about 0.5 seconds and P1 increased concomitantly by about 2cmH2O. After allowing sufficient time for these adjustments to takeeffect on the patient, PaCO2 should be re-evaluated. If the patientremains hypercarbic, T1 should be increased again by about 0.5 secondsand P1 again increased concomitantly by about 2 cmH2O. PaCO2 should thenbe reassessed and concomitant increases of about 0.5 seconds in T1 andabout 2 cmH2O in P1 repeated as indicated in FIG. 1 until the patient isno longer hypercarbic. However, the total duration of T1 should not beincreased beyond a maximum of about fifteen (15) seconds.

Management of oxygenation in accordance with the invention is carriedout with the goal of maintaining the level of oxygen in the arterialblood of the ventilated patient (PaO2) at a value of at least about 80mmHg and a maintaining saturation level (SaO2) of at least about 95%.Preferably fluctuation of PaO2 are held within a target range of about55 mmHg and 80 mmHg. (Expressed in terms of SpO2, the target range wouldbe between about 0.88 and 0.95 though where PaO2 and SpaO2 data are bothavailable, PaO2 would take precedence.) Responsive to a determinationthat oxygenation and saturation both meet the goals just specified, theventilator would be controlled to progressively decrease the fraction ofoxygen in the inspired gas (FiO2) by about 0.5 about every thirtyminutes to one hour with the objective of maintaining a blood oxygensaturation level (SaO2) of about 95% at a P1 of about 35 and an FiO2 ofabout 0.5. Upon meeting the latter objective, weaning in the manner tobe described may be initiated provided the ventilation goal describedearlier (i.e. a PaCO2 of less than about 50 mmHg) is met and weaning isnot otherwise contraindicated.

However, if the goals of oxygenation of PaO2 of at least about 80 mmHgand arterial blood oxygen saturation (SaO2) of at least about 95% cannotboth be maintained at the then-current FiO2, FiO2 is not decreased.Instead, P1 is increased to about 40 cmH2O and T1 increasedsubstantially contemporaneously by about 0.5 seconds. If such actiondoes not result in raising oxygenation and saturation to at least thegoals of about PaO2 of about 80 mmHg and SaO2 of about 95%, P1 isincreased to a maximum of about 45 cmH2O and T1 is progressively furtherincreased by about 0.5 seconds to 1.0 seconds. Oxygenation andsaturation are then re-evaluated and, if they remain below goal, FiO2,if initially less than 1.0, may optionally be increased to about 1.0.Oxygen and saturation continue to be re-evaluated and, T1 successivelyraised in increments of about 0.5 to 1.0 seconds until the stated oxygenand saturation goals are met.

Once those oxygenation and saturation goals are met, ventilation iscontrolled to maintain those goals while progressively decreasing FiO2and P1 toward the levels at which initiation of weaning can beconsidered. More particularly, P1 is decreased by about 1 cmH2O per hourwhile FiO2 is decreased by about 0.05 about every thirty (30) minuteswhile maintaining an oxygen saturation of at least about 95%.

Weaning according to the invention, unless otherwise contraindicated,may commence after the oxygenation and ventilation goals described abovehave been met. That is, when PaCO2 remains below about 50 mmHg and SaO2remains at least about 95% at a P1 of about 35 cmH2O and FiO2, ifpreviously higher, has been weaned to a level of not greater than about0.5. During weaning in accordance with the invention, T1 is controlledto sustain recruitment while P1 is reduced to gradually reduce airwaypressure. As FIG. 8 illustrates, this is achieved by carrying out aseries of successive incremental reductions in P1 while substantiallycontemporaneously¹ carrying out a series of successive incrementalincreases in T1 so as to induce gradual pulmonary stress relaxation asFIG. 3 illustrates. As a result, the pulmonary pressure versus volumecurve shifts progressively from its inspiratory limb to its expiratorylimb as illustrated in FIG. 4. In a preferred embodiment as illustratedin FIG. 1, weaning is carried out in two stages, the first of which ismore gradual than the second. During the first stage, P1 is reduced byabout 2 cmH2O about every hour. Substantially contemporaneously witheach reduction in P1, T1 is increased by about 0.5 to 1.0 seconds up to,but not in excess of a T1 of about 15 seconds in total duration. As P1is being reduced in the manner just described, the fraction of oxygen inthe inspired gas (FiO2) is also gradually reduced in accordance with P1.During the first stage of weaning, this gradual weaning of FiO2 iscarried out substantially in accordance with Table 1 of FIG. 1. When P1has been reduced to about 24 cmH2O and FiO2 weaned to about 0.4 with thepatient sustaining a blood oxygen saturation (SaO2) of at least about95% weaning may proceed to the more aggressive second stage.¹ The term “substantially contemporaneously” should not be construed tobe limited to necessarily require that changes occur precisely at thesame moment. Rather, the term is to be construed broadly to encompassnot merely events that occur at the same time, but also any which areclose enough in time to achieve the advantages or effects described.

During the second stage, as FIG. 1 indicates, successive reductions inP1 and substantially contemporaneous increases in T1 continue about onceevery hour. However, during the second stage, the reductions in P1 takeplace in increments of about 4 cmH2O and the increases in T1 are eachabout 2.0 seconds. As reductions in P1 continue, further weaning of FiO2is implemented substantially in accordance with Table 2 of FIG. 1. OnceFiO2 is weaned to about 0.3, airway pressures are reduced such that theventilation mode by then has been transitioned from APRV to asubstantially Continuous Positive Airway Pressure/Automatic TubeCompensation Mode (CPAP/ATC).

Once the patient is tolerating CPAP at about 5 cmH2O with FiO2 of notgreater than about 0.5, the patient's ability to maintain unassistedbreathing is assessed, preferably for at least about 2 hours or more.

-   -   a.) SpO2 of at least about 0.90 and/or PaO2 of at least about 60        mmHg;    -   b.) tidal volume of not less than about 4 ml/kg of ideal        bodyweight;    -   c.) respiration rate not significantly above about 35 breaths        per minute, and    -   d.) lack of respiratory distress, with such distress being        indicated by the presence of any two or more of the following:    -   i) Heart rate greater than 120% of the 0600-hour rate (though        less than about 5 minutes above such rate may be considered        acceptable)    -   ii) marked use of accessory muscles to assist breathing;    -   iii) thoroco-abdominal paradox;    -   iv) diaphoresis and/or    -   v) marked subjected dyspnea.

If there is an indication of respiratory distress, CPAP at an airwaypressure of about 10 cmH2O should be resumed and monitoring andreassessment carried out as needed. However, if criteria a) through d)above are all satisfied, the patient may be transitioned tosubstantially unassisted breathing such as by extubation with face mask,nasal prong oxygen or room air, T-tube breathing, tracheotomy maskbreathing or use of high flow CPAP at about 5 cmH2O.

During all phases of ventilation including initiation, management andweaning, the patent should be reassessed at least about every two hoursand more frequently if indicated. Blood gas measurements (PaO2 and SaO2and PaCO2) that govern control of ventilation according to the inventionshould be monitored not less frequently than every two hours thoughsubstantially continuous monitoring of all parameters would beconsidered ideal.

Just prior to and during weaning at least one special assessment shouldbe conducted daily, preferably between 0600 and 1000 hours. If notpossible to do so, a delay of not more than about four hours could betolerated. Weaning should not be initiated or continued further unless:

-   -   a) at least about 12 hours have passed since initial ventilation        settings were established or first changed,    -   b) the patient is not receiving neuromuscular blocking agents        and is without neuromuscular blockade, and    -   c) Systolic arterial pressure is at least about 90 mmHg without        vasopressors (other than “renal” dose dopamine).

If these criteria are all met, a trial should be conducted byventilating the patient in CPAP mode at about 5 cmH2O and an FiO2 ofabout 0.5 for about five (5) minutes. If the respiration rate of thepatient does not exceed about 35 breaths per minute (bpm) during thefive (5) minute period weaning as described above may proceed. However,if during the five (5) minute period the respiration rate exceeds about35 bpm it should be determined whether such tachypnea is associated withanxiety. If so, administer appropriate treatment for the anxiety andrepeat the trial within about four (4) hours. If tachypnea does notappear to be associated with anxiety, resume management of ventilationat the parameter settings in effect prior to the trial and resumemanagement of ventilation as described above. Re-assess at least dailyuntil weaning as described above can be initiated.

1-14. (canceled)
 15. A method of controlling a ventilator apparatuscomprising the steps of: a) placing a ventilator in a mode capable ofadjusting airway pressure (P) and time (T); b) monitoring expiratory gasflow; c) analyzing the expiratory gas flow over time (T) to establish anexpiratory gas flow pattern, and d) setting a low time (T2) based on theexpiratory gas flow pattern.
 16. The method of claim 15, furthercomprising the steps of monitoring inspiratory gas flow and determiningexpiratory and inspiratory gas volume.
 17. A method of controlling aventilator apparatus comprising the steps of placing a ventilator in amode capable of adjusting airway pressure (P) and time (T), and settinga low airway pressure (P2) of substantially zero cmH₂O.
 18. The methodof claim 17, further comprising the steps of: a) monitoring expiratorygas flow, b) analyzing the expiratory gas flow over time to establish anexpiratory gas flow pattern, and c) setting a low (T2) based on theexpiratory gas flow pattern.
 19. The method of claim 17, furthercomprising the steps of: a) monitoring expiratory and inspiratory gasflow, b) determining the relationship between the expiratory andinspiratory gas flow, and c) setting a high airway pressure (P1). 20.The method of claim 19, wherein the step of determining the relationshipcomprises determining the relationship comprises determining the ratioof the expiratory gas flow and the inspiratory gas flow.
 21. The methodof claim 19, further comprising the steps of analyzing the expiratoryand inspiratory gas flow over time (T) to establish an expiratory andinspiratory gas flow pattern and analyzing the expiratory andinspiratory gas flow pattern.
 22. The method of claim 17, wherein themode comprises a preset continuous positive airway pressure (CPAP) levelmode with an intermittent pressure release.
 23. The method of claim 22,further comprising the step of substantially simultaneously adjusting ahigh airway pressure (P1) and a high time (T1).
 24. The method of claim17, further comprising the steps of: a) monitoring blood carbon dioxidelevels for hypocarbia, b) increasing a high time (T1) and maintaining ahigh pressure (P1) substantially unchanged.
 25. The method of claim 17,further comprising the steps of: a) monitoring blood oxygen levels, andb) increasing a high airway pressure (P1) and a high time (T1)substantially contemporaneously to raise oxygenation levels.
 26. Themethod of claim 25, wherein P1 is increased to a maximum of about 45cmH₂0.
 27. The method of claim 26, further comprising the steps ofsubsequently decreasing P1 at a rate of about 1 cmH₂0 per hour andmaintaining oxygen levels.
 28. The method of claim 18, furthercomprising the step of controlling the ventilator with a control unit.29. The method of claim 28, wherein the control unit is programmed toanalyze the expiratory gas flow over time.
 30. A method of controlling aventilator apparatus comprising the steps of: a) placing a ventilator ina mode capable of adjusting airway pressure (P) and time (T), b) settinga low airway pressure (P2) of substantially zero cmH₂O c) monitoringblood CO₂ levels, and d) increasing the high time (T1) interval anddecreasing the high airway pressure (P1).
 31. The method claim 30,wherein the monitoring comprises determining whether the blood CO₂levels are normal or below normal.
 32. A method of controlling aventilator apparatus comprising the steps of: a) placing a ventilator ina mode capable of adjusting airway pressure (P) and time (T), and b)setting low airway pressure (P2) of no more than zero cmH₂O.